SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Fucoidan enhances the effect of chemotherapeutic drug against drug-resistant lung cancer cells.

Development of adjuvant chemotherapy drugs against drug-resistant lung cancer cells is necessary. The use of non-toxic adjuvant natural product combined with chemotherapy drugs will be an important treatment mode in the future. The purpose of the study investigates that fucoidan enhances chemotherapy drug poisoning drug-resistant lung cancer cell. Drug-resistant lung cancer cells are established in the study. Cell culture, MTT assay, wound healing assay, gelatin zymography assay, DNA fragmentation assay, apoptosis assay, reverse transcription polymerase chain reaction (RT-PCR) western blot analysis was adopted. The results showed that fucoidan synergized with doxorubicin increased efficacy of poisoning drug-resistant lung cancer cells and enhanced the ability of doxorubicin to inhibit the migration of drug-resistant lung cancer cells. It was observed that fucoidan synergized with doxorubicin induced the increase of apoptosis and inhibited expression of MMP-9, LC3, Beclin-1 and ß-catenin in drug-resistant lung cancer cells. Fucoidan synergized with doxorubicin significantly inhibited proliferation, migration and metastasis of drug-resistant lung cancer cells. Fucoidan strengthened doxorubicin to induce apoptosis and autophagy of drug-resistant lung cancer cells. This study confirms that the combined use of fucoidan and chemotherapeutic drugs can effectively poison drug-resistant lung cancer cells.

Fabrication of Biodegradable Poly(caprolactone) Spherical-Microcarriers for Arterial Embolization.

This study aimed to develop emulsification assisted with ultrasonic atomization (EUA) to make embolic biodegradable poly(caprolactone) (PCL) spherical-microcarriers with uniform particle size for mass production which was used to cure hepatocellular carcinoma, because this kind of embolic drugs is expensive at the current market due to their complex manufacturing process. The embolic spherical-microcarriers with sustained-releasing therapeutic agents can shrink an unresectable tumor into a respectable size. Through high frequency vibrating surface on the ultrasonic atomizer nozzle, the thin liquid film for PCL oil-phase solution was broken into the uniform PCL microdroplets (particle sizes are from 20 to 55 µm) with less medicine loss. To determine the optimal parameters to make PCL microcarriers, the ultrasonic module parameters including the concentration of PCL solution, vibrating amplitude of atomizer, feeding rate of PCL oil-phase solution and collection distance on the particle size of microdroplets were analyzed. Besides, a vertical circulation flow field of aqueous-phase poly(vinyl alcohol) (PVA) solution was created to enhance the separation of the microdroplets and increase the production of the PCL microcarriers, and about 8~11 wt% of PVA solution with high stable dispersion property was used to effectively improve the yield rate of PCL spherical-microcarriers (89.8~98.2 wt%). The final particle size of PCL microcarriers was ca. 5-18 µm, indicating an about 25-50% volume shrinkage from microdroplets to solid spherical-microcarriers.

Cancer Biology Aspects of Computational Methods & Applications in Drug Discovery.

BACKGROUND: Cancer is one of the most debilitating diseases worldwide; even though advances in molecular and cellular biology have contributed to the decline of mortality associated with cancer, the procedure of drug discovery and development of cancer are time-consuming and expensive. However, with computer-aided drug discovery (CADD) techniques, pharmaceutical firms can save production costs and reduce the time of introducing effective anticancer drugs for clinical trials. CADD strategies like structure-based drug designing, ligandbased drug designing, and combined structure-based and ligand-based approaches also have the advantage of identifying target sites and discovering active compounds with high affinity for the target sites. In this article, research carried out on cancer biology aspect of the computational approaches in drug discovery technology have been reviewed. OBJECTIVE: The main objective of the study is to identify the potential causes and the development of the cancer. In addition to this, its recovery has been discussed briefly. CONCLUSION: Our findings indicate that only a few studies have been carried out regarding this area. Hence, it is recommended that further researches should be conducted on the computational methods for identifying candidate drugs for breast, pancreatic, colon, prostate, and other types of cancer.

Downregulation of nuclear and cytoplasmic Chibby is associated with advanced cervical cancer.

Chibby has been identified as a putative tumor suppressor and antagonist to ß-catenin, thereby controlling the Wnt signaling pathway. Chibby is typically downregulated in numerous types of cancer and may be associated with tumorigenesis. The present study aimed at clarifying the following: i) Whether Chibby antagonizes ß-catenin in cervical cancer; ii) whether Chibby and ß-catenin mRNA expression is associated with cancer progression; and iii) whether Chibby and ß-catenin expression may be used as a biomarker. A total of 87 paraffin-embedded cervical sections with distinct cervical intraepithelial neoplasia (CIN) stages (chronic cervicitis, CIN 1, CIN 2, CIN 3 and invasive squamous cell carcinoma) were collected between June 2004 and October 2012 The mRNA expression level of Chibby and ß-catenin was determined using the polymerase chain reaction. Protein expression and cellular localization of Chibby and ß-catenin were determined using immunohistochemistry. Chibby and ß-catenin were analyzed for possible association with the progression of cervical cancer. Chibby mRNA expression and the Chibby/ß-catenin ratio were identified to be downregulated in invasive tumors. Positive cytoplasmic and nuclear staining for Chibby was associated with CIN staging and decreased as the CIN stage increased. In addition, the cytoplasmic and membrane intensity of ß-catenin was associated with invasive tumors, in which a significantly increased level of protein expression was detected. Chibby may be a tumor suppressor in cervical cancer, since the dysregulation of Chibby expression is associated with tumorigenesis in cervical cancer. Chibby and ß-catenin expression together may potentially to a biomarker for disease progression in cervical cancer.

A microtubule inhibitor, ABT-751, induces autophagy and delays apoptosis in Huh-7 cells.

The objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel anti-microtubule drug, ABT-751, in hepatocellular carcinoma-derived Huh-7 cells. Effects of ABT-751 were evaluated by immunocytochemistry, flow cytometric, alkaline comet, soft agar, immunoblotting, CytoID, green fluorescent protein-microtubule associated protein 1 light chain 3 beta detection, plasmid transfection, nuclear/cytosol fractionation, coimmunoprecipitation, quantitative reverse transcription-polymerase chain reaction, small-hairpin RNA interference and mitochondria/cytosol fractionation assays. Results showed that ABT-751 caused dysregulation of microtubule, collapse of mitochondrial membrane potential, generation of reactive oxygen species (ROS), DNA damage, G2/M cell cycle arrest, inhibition of anchorage-independent cell growth and apoptosis in Huh-7 cells. ABT-751 also induced early autophagy via upregulation of nuclear TP53 and downregulation of the AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (MTOR) pathway. Through modulation of the expression levels of DNA damage checkpoint proteins and G2/M cell cycle regulators, ABT-751 induced G2/M cell cycle arrest. Subsequently, ABT-751 triggered apoptosis with marked downregulation of B-cell CLL/lymphoma 2, upregulation of mitochondrial BCL2 antagonist/killer 1 and BCL2 like 11 protein levels, and cleavages of caspase 8 (CASP8), CASP9, CASP3 and DNA fragmentation factor subunit alpha proteins. Suppression of ROS significantly decreased ABT-751-induced autophagic and apoptotic cells. Pharmacological inhibition of autophagy significantly increased the percentages of ABT-751-induced apoptotic cells. The autophagy induced by ABT-751 plays a protective role to postpone apoptosis by exerting adaptive responses following microtubule damage, ROS and/or impaired mitochondria.

Original Research: Porcine model for observing changes due to ischemia/reperfusion injury secondary to intra-abdominal endovascular balloon occlusion.

Compared with conventional aortic cross-clamping, endovascular balloon occlusion (EBO) is a valuable strategy in unstable ruptured abdominal aorta aneurysm patients; however, it is unclear how long the balloon may remain safely inflated. Using a porcine model, we evaluated the influence of different EBO time periods on intra-abdominal pressure (IAP) and the association between various pathophysiologic indicators and reperfusion time. Twelve healthy three-month-old domestic piglets were subjected to ischemia/reperfusion injury using EBO within the abdominal aorta. Animals were grouped as A, B, and C based on 30, 60, or 120 min of ischemic time, respectively. Changes in IAP, hemodynamic data, respiratory and renal function, and histology after reperfusion were compared with baseline measurements. All pigs gradually developed intra-abdominal hypertension after ischemia/reperfusion injury. IAP increased significantly after 4 h of reperfusion in all three groups (all P < 0.001) with maximal IAP reaching > 22 mmHg in 10 pigs. However, no significant intergroup differences were found. Cardiac output remained stable, but mixed venous oxygen saturation decreased significantly at 4 h after reperfusion (P < 0.05). The pH decreased significantly at 10 min in all three groups (all P < 0.001). Histological changes in the small intestine, lung, and kidney occurred secondary to aortic ischemia; however, no significant differences were noted between groups (P > 0.05). EBO within the abdominal aorta induced ischemia/reperfusion injury which led to intra-abdominal hypertension, pathological changes within multiple organs, and decreased mixed venous oxygen saturation after only 30 min of abdominal aortic ischemia.

Emphysematous cholecystitis presenting as gas-forming liver abscess and pneumoperitoneum in a dialysis patient: a case report and review of the literature.

BACKGROUND: Emphysematous cholecystitis is a rare variant of acute cholecystitis with a high mortality rate. The combination of emphysematous cholecystitis, liver abscess and pneumoperitoneum are even rarer. Herein we present a case of emphysematous cholecystitis in a senile diabetic lady who had worsening hemodynamics while undergoing hemodialysis. CASE PRESENTATION: A 64-year-old woman with history of type 2 diabetes mellitus and end stage renal disease with regular hemodialysis presented to the emergency department with a 1-day history of sudden onset of lassitude and hypotension during hemodialysis. The result of a computed tomography (CT)-scan revealed air encircling the gallbladder, liver parenchymal and minimal pneumoperitoneal and liver abscess with no cholelithiasis. The patient had received empirical antibiotics with piperacillin-tazobactam 2.25 g intravenous route every 6 h for 14 days and cholecystectomy with surgical debridement and lead an uneventful postoperative hospital course. Escherichia coli was demonstrated as well as blood culture and peritoneal fluid culture. CONCLUSION: In a senile diabetic and dialysis patient, we should take emphysematous cholecystitis into consideration once vague abdominal pain occurrs. Empirical antibiotic therapy and adequate surgical intervention should take place as soon as possible.

Urethral Metastasis from Rectal Adenocarcinoma: A Case Report and Review of the Literature.

CASE: A 73-year-old man with Dukes' C adenocarcinoma of the rectum, pT3N2bM0, stage IIIB, presented with voiding difficulties including poor stream and terminal dribbling for one month. The patient was under careful surveillance and had no postoperative recurrence. Physical examination revealed a palpable irregular nodular lesion (0.5 × 0.5 cm(2)) at the penile-scrotal junction. He underwent urethroscopy, which showed a cauliflower lesion in the pendulous urethra. Transurethral resection was performed and histopathologic and immunochemical staining demonstrated a metastatic moderately differentiated urethral adenocarcinoma from the colorectal primary. OUTCOME: His voiding disorder improved significantly post-operation and he commenced second-line chemotherapy combined with regional radiotherapy. Follow-up urethrocystoscopy and abdominal computed tomography demonstrated no recurrence or metastatic disease. His tumor marker remained within the normal range for 12 months. CONCLUSION: Urethral metastasis from primary colon cancer is extremely rare. This disease, with its various atypical presentations, presents a diagnostic challenge to the clinician. In patients with recurrent or persistent lower urinary tract symptoms, further urologic workup including thorough history taking, physical examination, and imaging surveys is warranted.

Molecular Characterization of Community- and Healthcare-Associated Methicillin-Resistant Staphylococcus aureus Isolates in Southern Taiwan.

A growing tendency for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) to be involved in nosocomial infections was reported. The predominance of SCCmec type IV or V CA-MRSA in soft tissue infection has also been indicated in Northern Taiwan. To establish basic information about the molecular characteristics of MRSA in our region, a total of 102 MRSA isolates were collected and characterized by an array of typing methods. Healthcare-associated MRSA (HA-MRSA) were found to be more resistant to levofloxacin (p=0.016) and moxifloxacin (p=0.015) than CA-MRSA. However, no difference was found in each and overall SCCmec type distribution between the two MRSA groups. Type I (8.7% vs. 2.6%) was more frequently found in CA-MRSA, whereas type V was more often observed in HA-MRSA (24.4% vs. 8.7%). No difference was found in the dichotomous group of PVL, SCCmec type IV, V, and IV/V between the two MRSA groups. Twenty-seven distinct spa types were identified; t437 and t1081 were the predominant types in our isolates. Moreover, 12 novel spa types with extremely low global frequency were detected in our isolates. SCCmec type III and IV were the major subtypes in the MRSA we collected. The t1081 clones all belonged to HA-MRSA and mostly to SCCmec type V (71.4%). CA-MRSA t437 clones were mostly SCCmec type IV strains (71.4%), but HA-MRSA t437 clones were predominantly SCCmec type IV (42.1%) and III (36.8%). Our findings support a difference in the molecular characteristics of CA-MRSA and HA-MRSA that may reflect various clonal origins in our isolates.

Differential roles of Bcl2L12 and its short variant in breast cancer lymph node metastasis.

Bcl2L12 plays a role in post-mitochondrial apoptosis through multiple mechanisms involving p53, αB-crystallin, caspase-3 and -7 in glioblastoma. Bcl2L12 is reported to be a good prognostic marker in breast cancer and correlated with ER and Bcl2 expression status. However, the mechanisms by which Bcl2L12 regulates apoptosis in breast cancer (BCa) remain unknown. Recent studies have shown that Bcl2L12 expression is a useful biomarker in other types of cancer. Thus, we examined whether Bcl2L12 and Bcl2L12A mRNA were associated with breast cancer progression or a specific subtype. In total, 106 paraffin-embedded, different stage breast cancer specimens were prepared and quantified for Bcl2L12 and Bcl2L12A expression by PCR. The correlation between Bcl2L12 and Bcl2L12A mRNA levels and clinicopathological characteristics was statistically analyzed. The results showed that Bcl2L12 and Bcl2L12A mRNA expression was not significantly different across the different stage, grade and TNM classification groups (P>0.005). Using linear regression, Bcl2L12 mRNA was associated with Bcl2L12A mRNA, grade 3 tumor and the triple-negative breast cancer (TNBC) subtype. In non-TNBC specimens, Bcl2L12 mRNA was only correlated with Bcl2L12A mRNA. Bcl2L12A mRNA was positively associated with Bcl2L12 mRNA and the number of lymph node metastases, but negatively correlated with staging in the non-TNBC group. Specifically, Bcl2L12, but not Bcl2L12A, mRNA was significantly higher in TNBC and grade 3 tumors, respectively. In non-TNBC, Bcl2L12A mRNA was significantly highly expressed in tumors with ≥ 12 metastatic lymph nodes. Bcl2L12 and its variant mRNA were highly expressed in carcinoma in situ (CIS) samples. In addition, they were estimated to be correlated with the total sample and non-TNBC, but not the TNBC group. In summary, a high Bcl2L12 mRNA expression was associated with the high-grade BCa and TNBC subtype. In addition, the interplay between Bcl2L12 and its variant may be associated with high lymph node metastasis in non-TNBC tumors.

Galangin, a novel dietary flavonoid, attenuates metastatic feature via PKC/ERK signaling pathway in TPA-treated liver cancer HepG2 cells.

BACKGROUND: Galangin (3,5,7-trihydroxyflavone) is a flavonoid compound found in high concentration in lesser galangal. The objective of this study was to investigate the ability of galangin to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced the invasion and metastasis of HepG2 liver cancer cells. RESULTS: First, using a cell-matrix adhesion assay, immunofluorescence assay, transwell-chamber invasion/migration assay, and wound healing assay, we observed that galangin exerted an inhibitory effect on TPA-induced cell adhesion, morphology/actin cytoskeleton arrangement, invasion and migration. Furthermore, the results of gelatin zymography and reverse transcriptase polymerase chain reaction (RT-PCR) assays showed that galangin reduced the TPA-induced enzyme activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in HepG2 cells; moreover, the messenger RNA level was downregulated. We also observed through a Western blotting assay that galangin strongly inhibited the TPA-induced protein expressions of protein kinase Cα (PKCα), protein kinase Cδ (PKCδ), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), the phospho-inhibitor of kappaBα (phospho-IκBα), c-Fos, c-Jun, and nuclear factor kappa B (NF-κB). Next, galangin dose-dependently inhibited the binding ability of NF-κB and activator protein 1 (AP-1) to MMP-2/MMP-9 promoters, respectively, resulting in the suppression of MMP-2/MMP-9 enzyme activity. CONCLUSIONS: The results revealed that galangin effectively inhibited the TPA-induced invasion and migration of HepG2 cells through a protein kinase C/extracellular signal-regulated kinase (PKC/ERK) pathway. Thus, galangin may have widespread applications in clinical therapy as an anti-metastatic medicament.

Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

Lobular capillary hemangioma of the nasal cavity: a retrospective study of 15 cases in taiwan.

BACKGROUND: Lobular capillary hemangioma of the nasal cavity is an uncommon benign vascular tumor of unknown etiology. There have been only very few case reports in Taiwan. AIMS: This study aimed to analyze the clinical features, radiological findings, treatment modalities, and outcome of lobular capillary hemangioma treated at a teaching hospital in Taiwan during a period of 10 years. STUDY DESIGN: Descriptive study. METHODS: Retrospective chart reviews were performed on patients who were diagnosed with lobular capillary hemangioma of the nasal cavity at Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, from January 2003 to December 2012. Data retrieved included age, gender, clinical symptoms, computed tomography (CT) findings, treatment modalities, and outcome for further analysis. RESULTS: Of the 15 patients identified, there were five males and ten females ranging from 17 to 86 years of age, with a mean age of 43.8±20.2. Epistaxis was the most common presenting symptom. All patients presented a unilateral nasal lobular capillary hemangioma. The most commonly affected site was the anterior nasal septum, followed by the inferior turbinate, vestibule, middle turbinate, and posterior nasal septum. All lesions presented as soft tissue density without bony erosions under CT examination. Endoscopic excisional surgery (n=12) or classical local excision (n=3) was performed for complete removal of the hemangioma. No evidence of recurrence was observed with 6 to 75 months of follow-up. CONCLUSION: Lobular capillary hemangioma of the nasal cavity was usually found to occur in anterior septum with epistaxis. Complete excision with endoscopic surgery or classical local excision was recommended and recurrence can be prevented.

The activity of lowering intraocular pressure of cassiae seed extract in a DBA/2J mouse glaucoma model.

PURPOSE: To evaluate the activity of lowering intraocular pressure (IOP) by Cassiae seed in the DBA/2J mouse glaucoma model. METHODS: Young male (mean age: 3 months) inherited glaucoma mice (BDA/2J) were enrolled in this study. To evaluate the potential of Cassiae seed in the treatment of glaucoma, all subjects were divided into 6 groups. There were 1 sham group, positive control identified as group 2 topical brimonidine and group 3 oral acetazolamide, and groups 4-6 Cassiae seed extract (CSE) groups. The lactate dehydrogenase (LDH) level in the anterior aqueous humor and the changes of IOP were investigated. Contents of total polyphenol glycosides in the CSE were measured using a high-performance liquid chromatography (HPLC) method. Chromatographic separation was performed on a Cosmosil 5C(18)-MS reverse-phase HPLC column (4.6×250-mm i.d., 5 µm) with methanol/0.1% H(3)PO(4) as the mobile phases in a gradient elution mode at a flow rate of 1.0 mL/min and an injection volume of 10 µL. The wavelength of UV detector was set at 254 nm. RESULTS: The LDH level in the anterior aqueous humor and IOP significantly decreased after treatment with CSE. The IOP-lowering effect of CSE was comparable to those of oral acetazolamide and brimonidine instillation. There were no abnormal findings in the external appearance, and body weight change after treatment with CSE for 5 weeks. Chrysophanol and physcion were measured by an HPLC method to obtain total polyphenol glycosides of the CSE, and were involved in the IOP-lowering function. CONCLUSION: Cassiae seed may be safe and beneficial for treating glaucoma due to its significant IOP- and LDH-lowering activities.

Molecular characterisation of multiple drug-resistant Acinetobacter baumannii isolates in southern Taiwan.

The purpose of this study was to develop a multiplex polymerase chain reaction (mt-PCR) assay for synchronous detection of carbapenem resistance genes and/or pandrug resistance genes in clinical isolates of multidrug-resistant Acinetobacter baumannii (MDR-AB) and to investigate the association between the genetic make-up and a drug-resistant pattern. In total, 213 MDR-AB isolates were collected. All clinical isolates underwent antimicrobial susceptibility testing and were analysed for the presence of oxacillinase genes (bla(OXA-23), bla(OXA-24), bla(OXA-51)-like and bla(OXA-58)), class A and C ß-lactamase genes (bla(TEM-1) and bla(AmpC), respectively), and an integron-associated antibiotic resistance gene (int1) by an in-house-designed mt-PCR assay. Of the 213 isolates, 73.87% harboured both bla(TEM-1) and bla(AmpC) and 83.92% carried at least three oxacillinase genes. Moreover, 64.82% of the isolates were significant in that they had two ß-lactamase genes and three oxacillinase genes (P<0.001), indicating the complexity of the genetic make-up of carbapenem-resistant A. baumannii. The bla(OXA-51)-like allele was detected in the majority of these A. baumannii isolates (97.49%), whereas bla(OXA-23) was rarely prevalent in these isolates. In multivariate logistic regression, the presence of bla(OXA-23) and bla(TEM-1) had a statistically significant association with imipenem resistance [bla(OXA-23), P=0.004, odds ratio (OR)=10.52, 95% confidence interval (CI) 2.12-52.17; bla(TEM-1), P=0.005, OR=6.14, 95% CI 1.74-21.62]. These results suggest that detecting bla(OXA-23) and bla(TEM-1) genes could be used to predict imipenem resistance in MDR-AB isolates. A mt-PCR for detecting carbapenem resistance genes and pandrug resistance genes of A. baumannii isolates was developed to provide an assay to quickly screen for potential imipenem-resistant A. baumannii in the clinic.

Acacetin inhibits the invasion and migration of human non-small cell lung cancer A549 cells by suppressing the p38α MAPK signaling pathway.

Lung cancer is one of the most common malignancies in the world and its metastasis is the major cause of death in cancer patients. Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on invasion and migration in human NSCLC A549 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by cell-matrix adhesion assay, immunofluorescence assay, Boyden chamber assay, and wound-healing assay. Molecular data showed that the effect of acacetin in A549 cells might be mediated via sustained inactivation of the phosphorylation of mixed-lineage protein kinase 3 (MLK3), mitogen-activated protein kinase kinases 3/6 (MKK3/6), and p38α MAPK signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA). Next, acacetin significantly decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), and the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, the treatment with acacetin to A549 cells also leads to a concentration-dependent inhibition on the binding abilities of NF-κB and activator protein-1 (AP-1). Furthermore, the treatment of specific inhibitor for p38 MAPK (SB203580) to A549 cells could cause reduced activities of MMP-2/9 and u-PA. In addition, acacetin significantly decreased the levels of phospho-p38α MAPK, MMP-2/9, and u-PA in p38α-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Our results revealed the anti-migration and anti-invasion effects of acacetin, which may act as a promising therapeutic agent for the treatment of lung cancer.

Alpha-mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via alphavbeta3 integrin/FAK/ERK and NF-kappaB signaling pathway in human lung adenocarcinoma A549 cells.

The purpose of this study is to investigate the anti-metastatic effect of alpha-mangostin on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in A549 human lung adenocarcinoma cells. Firstly, alpha-mangostin could inhibit PMA-induced abilities of the adhesion, invasion, and migration. Data also showed alpha-mangostin could inhibit the activation of alphavbeta3 integrin, focal adhesion kinase (FAK), and extracellular signal-regulated kinase1/2 (ERK1/2) involved in the downregulation the enzyme activities, protein and messenger RNA levels of MMP-2 and MMP-9 induced by PMA. Next, alpha-mangostin also strongly inhibited PMA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels of nuclear factor kappa B (NF-kappaB). Also, a dose-dependent inhibition on the binding abilities of NF-kappaB by alpha-mangostin treatment was further observed. Furthermore, reduction of FAK or ERK1/2 phosphorylation by FAK small interfering RNA (FAK siRNA) potentiated the effect of alpha-mangostin. Finally, the transient transfection of ERK siRNA significantly down-regulated the expressions of MMP-2 and MMP-9 concomitantly with a marked inhibition on cell invasion and migration. Presented results indicated alpha-mangostin is a novel, effect, anti-metastatic agent that functions by downregulating MMP-2 and MMP-9 gene expressions.

Collecting factors related to the haemolysis of blood specimens.

AIM: The purpose of the study is to explore the collecting factors for the haemolysis of the blood specimens in a regional hospital in South Taiwan. BACKGROUND: Blood collecting is one of the most common procedures used in hospital. However, it often faces the risk of haemolysis of blood specimens during laboratory testing and the specimens collected can be easily rejected by the laboratory. METHODS: This is a descriptive and cross-sectional study. The purposive samples were collected from the blood specimens of the hospitalized patients or the emergency-room patients by using structured observational checklists which included demographic characteristics, caring factors and material factors. A total of 274 blood specimens was collected. RESULTS: Specimens obtained from non-antecubital sites were 3.35 times at risk of haemolysis as many as those from antecubital sites (p = 0.001). Blood collected into tubes through steel needles were 3.7 times more at risk of haemolysis as that through syringes (after removing needles) (p = 0.002). Specimens delivered by ward assistants were 8.7 times more at risk for haemolysis as those by the laboratory staff (p < 0.01). CONCLUSIONS: These findings suggest that nurse supervisors establish a protocol related to preventing haemolysis. Future research should explore the effectiveness of this protocol to verify the relationship between different gauges of steel needles or catheters and haemolysis. RELEVANCE TO CLINICAL PRACTICE: Nurse educators are encouraged to include the factors affecting and preventing haemolysis into the in service education. Therefore, findings may assist healthcare professionals in minimizing the risk of haemolysis and improve the quality of care.